Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model.

Abstract

Peloruside A is a microtubule-stabilizing agent isolated from a New Zealand marine sponge. Peloruside prevents growth of a panel of cancer cell lines at low nanomolar concentrations, including cell lines that are resistant to paclitaxel. Three xenograft studies in athymic nu/nu mice were performed to assess the efficacy of peloruside compared with standard anticancer agents such as paclitaxel, docetaxel, and doxorubicin. The first study examined the effect of 5 and 10 mg/kg peloruside (QD×5) on the growth of H460 non-small cell lung cancer xenografts. Peloruside caused tumor growth inhibition (%TGI) of 84% and 95%, respectively, whereas standard treatments with paclitaxel (8 mg/kg, QD×5) and docetaxel (6.3 mg/kg, Q2D×3) were much less effective (%TGI of 50% and 18%, respectively). In a second xenograft study using A549 lung cancer cells and varied schedules of dosing, activity of peloruside was again superior compared with the taxanes with inhibitions ranging from 51% to 74%, compared with 44% and 50% for the two taxanes. A third xenograft study in a P-glycoprotein-overexpressing NCI/ADR-RES breast tumor model showed that peloruside was better tolerated than either doxorubicin or paclitaxel. We conclude that peloruside is highly effective in preventing the growth of lung and P-glycoprotein-overexpressing breast tumors in vivo and that further therapeutic development is warranted. Mol Cancer Ther; 14(8); 1816-23. ©2015 AACR.

• Authors: Colin J Meyer, Melissa Krauth, Michael J Wick, Jerry W Shay, Ginelle Gellert, Jef K De Brabander, Peter T Northcote, John H Miller
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 14 Issue 8 Pg. 1816-23 (Aug 2015) ISSN: 1538-8514 [Electronic] United States
• PMID: 26056149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Lactones
• Taxoids
• peloruside A
• Docetaxel
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Bridged Bicyclo Compounds, Heterocyclic (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Docetaxel
• Female
• Humans
• Inhibitory Concentration 50
• Lactones (chemistry, pharmacology)
• Lung Neoplasms (drug therapy, pathology)
• Mice
• Mice, Nude
• Paclitaxel (pharmacology)
• Taxoids (pharmacology)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays